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Article ; Online: Endothelial cell-derived extracellular vesicles induce pro-angiogenic responses in mesenchymal stem cells.

Abdik, Hüseyin / Kırbaş, Oğuz Kaan / Bozkurt, Batuhan Turhan / Avşar Abdik, Ezgi / Hayal, Taha Bartu / Şahin, Fikrettin / Taşlı, Pakize Neslihan

FEBS open bio

2024 Volume 14, Issue 5, Page(s) 740–755

Abstract: Angiogenesis is a central component of vital biological processes such as wound healing, tissue nourishment, and development. Therefore, angiogenic activities are precisely maintained with secreted factors such as angiopoietin-1 (Ang1), fibroblast growth ...

Abstract	Angiogenesis is a central component of vital biological processes such as wound healing, tissue nourishment, and development. Therefore, angiogenic activities are precisely maintained with secreted factors such as angiopoietin-1 (Ang1), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF). As an element of intracellular communication, extracellular vesicles (EVs)-particularly EVs of vascular origin-could have key functions in maintaining angiogenesis. However, the functions of EVs in the control of angiogenesis have not been fully studied. In this study, human umbilical vein endothelial cell line (HUVEC)-derived small EVs (<200 nm; HU-sEVs) were investigated as a potential pro-angiogenic agent. Treating mesenchymal stem cells (MSCs) and mature HUVEC cells with HU-sEVs induced their tube formation under in vitro conditions and significantly increased the expression of angiogenesis-related genes, such as Ang1, VEGF, Flk-1 (VEGF receptor 2), Flt-1 (VEGF receptor 1), and vWF (von Willebrand Factor), in a dose-dependent manner. These results indicate that HU-sEVs take part in angiogenesis activities in physiological systems, and suggest endothelial EVs as a potential therapeutic candidate for the treatment of angiogenesis-related diseases.
MeSH term(s)	Humans ; Extracellular Vesicles/metabolism ; Mesenchymal Stem Cells/metabolism ; Human Umbilical Vein Endothelial Cells/metabolism ; Neovascularization, Physiologic ; Angiopoietin-1/metabolism ; Angiopoietin-1/genetics ; Cells, Cultured ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Angiopoietin-1 ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2024-03-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2651702-4
ISSN	2211-5463 ; 2211-5463
ISSN (online)	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.13650
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Lead Borate Nanoparticles Induce Apoptotic Gene Activity in P53 Mutant Cancer Cells

Hayal, Taha Bartu / Kırbaş, Oğuz Kaan / Bozkurt, Batuhan Turhan / Taşlı, Pakize Neslihan / Bülbül, Berna / Beyaz, Seda / Şahin, Fikrettin

Biological trace element research. 2022 Feb., v. 200, no. 2

2022

Abstract: Cancer is a complex and multistage disease that causes suffering worldwide. Several mutations in tumor suppressor proteins are mostly responsible for tumorigenic development. Thus, determination of the mutations and developing a mutation targeted therapy ...

Abstract	Cancer is a complex and multistage disease that causes suffering worldwide. Several mutations in tumor suppressor proteins are mostly responsible for tumorigenic development. Thus, determination of the mutations and developing a mutation targeted therapy are crucial in order to cure cancer. Moreover, since healthy cells do not have mutations in their tumor suppressor genes, mutation-specific treatment is responsible for selective treatment without harming a healthy tissue in the body. In this current study, lead borate nanoparticles (LB-Np) have been synthesized, and their effects on P53 mutant cancer cells were investigated. The synthesis method includes steps of mixing a borate buffer solution with the lead nitrate solution, washing the resulting precipitate with distilled water and eventually preparing stable LB-Np solutions. Cell viability analysis was conducted to identify the toxicity of LB-Np in HaCaT, A549, MCF7, and T47D cell lines. The changes in morphologies of breast cancer cell lines were demonstrated by using microscopical analysis. Additionally, alterations in gene expressions were determined in breast cancer cell lines after LB-Np treatment. This multidisciplinary study also identified the selective effect of LB-Np in cancer cell lines, in vitro. MTS and quantitative polymerase chain reaction assays demonstrated the effect of LB-Np were specific for p53 mutation cell line, T47D. Breast cancer cell line T47D has 580 C/T mutation which affects the activation of p53 tumor suppressor protein. However, LB-Np treatment effectively killed T47D cell lines and did not affect any other cell lines that have no p53 mutations such as MCF7, A549, and healthy HaCaT. Overall, synthesized LB-Np were found to be effective in p53-mutated cell lines and showed a remarkable selective anti-cancer activity.
Keywords	antineoplastic activity ; apoptosis ; borates ; breast neoplasms ; cell lines ; cell viability ; lead ; lead nitrate ; mutants ; mutation ; neoplasm cells ; quantitative polymerase chain reaction ; research ; therapeutics ; toxicity ; trace elements ; tumor suppressor protein p53
Language	English
Dates of publication	2022-02
Size	p. 574-581.
Publishing place	Springer US
Document type	Article
ZDB-ID	445336-0
ISSN	1559-0720 ; 0163-4984
ISSN (online)	1559-0720
ISSN	0163-4984
DOI	10.1007/s12011-021-02696-0
Database	NAL-Catalogue (AGRICOLA)

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Article: Grapefruit-derived extracellular vesicles as a promising cell-free therapeutic tool for wound healing

Savcı, Yağız / Kırbaş, Oğuz Kaan / Bozkurt, Batuhan Turhan / Abdik, Ezgi Avşar / Taşlı, Pakize Neslihan / Şahin, Fikrettin / Abdik, Hüseyin

Food & function. 2021 June 8, v. 12, no. 11

2021

Abstract: Due to the prevalence of individuals suffering from chronic wounds, developing safe and effective wound care agents are one of the more prominent fields of research in biology. However, wound healing is a complex, multi-stage biological process, ... ...

Abstract	Due to the prevalence of individuals suffering from chronic wounds, developing safe and effective wound care agents are one of the more prominent fields of research in biology. However, wound healing is a complex, multi-stage biological process, involving multiple sequences of biological responses from different types of cells, secreted mediators, and extracellular matrix elements. Plants have a long history of use in the treatment of wounds. Plant-derived extracellular vesicles, which are secreted nano vesicle messengers responsible for intercellular communications, show promise as a new, biotechnological wound-care agent. In this study, we assessed the wound healing potential of extracellular vesicles isolated from grapefruits – a plant with well-known anti-inflammatory and wound healing properties. Grapefruit extracellular vesicles (GEVs) increased cell viability and cell migration while reducing intracellular ROS production in a dose-dependent manner in HaCaT cells. Expression of proliferation and migration-related genes were raised by GEV treatment in a dose dependent manner. Additionally, GEV treatment increased the tube formation capabilities of treated HUVEC cells. These findings suggest that GEVs can be used as plant-derived wound healing agents, and have shown potential as a biotechnological agent for wound healing. Further development and study of plant-derived extracellular vesicles may lead to the realization of their full potential.
Keywords	cell movement ; cell viability ; dose response ; extracellular matrix ; grapefruits ; therapeutics
Language	English
Dates of publication	2021-0608
Size	p. 5144-5156.
Publishing place	The Royal Society of Chemistry
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2612033-1
ISSN	2042-650X ; 2042-6496
ISSN (online)	2042-650X
ISSN	2042-6496
DOI	10.1039/d0fo02953j
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Grapefruit-derived extracellular vesicles as a promising cell-free therapeutic tool for wound healing.

Savcı, Yağız / Kırbaş, Oğuz Kaan / Bozkurt, Batuhan Turhan / Abdik, Ezgi Avşar / Taşlı, Pakize Neslihan / Şahin, Fikrettin / Abdik, Hüseyin

Food & function

2021 Volume 12, Issue 11, Page(s) 5144–5156

Abstract	Due to the prevalence of individuals suffering from chronic wounds, developing safe and effective wound care agents are one of the more prominent fields of research in biology. However, wound healing is a complex, multi-stage biological process, involving multiple sequences of biological responses from different types of cells, secreted mediators, and extracellular matrix elements. Plants have a long history of use in the treatment of wounds. Plant-derived extracellular vesicles, which are secreted nano vesicle messengers responsible for intercellular communications, show promise as a new, biotechnological wound-care agent. In this study, we assessed the wound healing potential of extracellular vesicles isolated from grapefruits - a plant with well-known anti-inflammatory and wound healing properties. Grapefruit extracellular vesicles (GEVs) increased cell viability and cell migration while reducing intracellular ROS production in a dose-dependent manner in HaCaT cells. Expression of proliferation and migration-related genes were raised by GEV treatment in a dose dependent manner. Additionally, GEV treatment increased the tube formation capabilities of treated HUVEC cells. These findings suggest that GEVs can be used as plant-derived wound healing agents, and have shown potential as a biotechnological agent for wound healing. Further development and study of plant-derived extracellular vesicles may lead to the realization of their full potential.
MeSH term(s)	Anti-Inflammatory Agents/pharmacology ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Citrus paradisi/chemistry ; Cytokines/metabolism ; Extracellular Matrix ; Extracellular Vesicles/metabolism ; HaCaT Cells ; Human Umbilical Vein Endothelial Cells ; Humans ; Nanoparticles ; Plant Extracts/pharmacology ; Wound Healing/drug effects ; Wound Healing/genetics
Chemical Substances	Anti-Inflammatory Agents ; Cytokines ; Plant Extracts
Language	English
Publishing date	2021-05-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2612033-1
ISSN	2042-650X ; 2042-6496
ISSN (online)	2042-650X
ISSN	2042-6496
DOI	10.1039/d0fo02953j
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Article ; Online: Lead Borate Nanoparticles Induce Apoptotic Gene Activity in P53 Mutant Cancer Cells.

Hayal, Taha Bartu / Kırbaş, Oğuz Kaan / Bozkurt, Batuhan Turhan / Taşlı, Pakize Neslihan / Bülbül, Berna / Beyaz, Seda / Şahin, Fikrettin

Biological trace element research

2021 Volume 200, Issue 2, Page(s) 574–581

Abstract	Cancer is a complex and multistage disease that causes suffering worldwide. Several mutations in tumor suppressor proteins are mostly responsible for tumorigenic development. Thus, determination of the mutations and developing a mutation targeted therapy are crucial in order to cure cancer. Moreover, since healthy cells do not have mutations in their tumor suppressor genes, mutation-specific treatment is responsible for selective treatment without harming a healthy tissue in the body. In this current study, lead borate nanoparticles (LB-Np) have been synthesized, and their effects on P53 mutant cancer cells were investigated. The synthesis method includes steps of mixing a borate buffer solution with the lead nitrate solution, washing the resulting precipitate with distilled water and eventually preparing stable LB-Np solutions. Cell viability analysis was conducted to identify the toxicity of LB-Np in HaCaT, A549, MCF7, and T47D cell lines. The changes in morphologies of breast cancer cell lines were demonstrated by using microscopical analysis. Additionally, alterations in gene expressions were determined in breast cancer cell lines after LB-Np treatment. This multidisciplinary study also identified the selective effect of LB-Np in cancer cell lines, in vitro. MTS and quantitative polymerase chain reaction assays demonstrated the effect of LB-Np were specific for p53 mutation cell line, T47D. Breast cancer cell line T47D has 580 C/T mutation which affects the activation of p53 tumor suppressor protein. However, LB-Np treatment effectively killed T47D cell lines and did not affect any other cell lines that have no p53 mutations such as MCF7, A549, and healthy HaCaT. Overall, synthesized LB-Np were found to be effective in p53-mutated cell lines and showed a remarkable selective anti-cancer activity.
MeSH term(s)	Borates/pharmacology ; Cell Line, Tumor ; Humans ; Lead/toxicity ; Mutation ; Nanoparticles ; Neoplasms ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Proteins
Chemical Substances	Borates ; Tumor Suppressor Protein p53 ; Tumor Suppressor Proteins ; Lead (2P299V784P)
Language	English
Publishing date	2021-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	445336-0
ISSN	1559-0720 ; 0163-4984
ISSN (online)	1559-0720
ISSN	0163-4984
DOI	10.1007/s12011-021-02696-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Effective Scarless Wound Healing Mediated by Erbium Borate Nanoparticles

Kırbaş, Oğuz Kaan / Bozkurt, Batuhan Turhan / Taşlı, Pakize Neslihan / Hayal, Taha Bartu / Özkan, İrem / Bülbül, Berna / Beyaz, Seda / Şahin, Fikrettin

Biological trace element research. 2021 Sept., v. 199, no. 9

2021

Abstract: The developments of nanoparticle-based treatments that benefit from novel discoveries have an essential place in the regeneration of acute and chronic wounds. Furthermore, research about the treatment methods which attempt to swiftly and scarless wound ... ...

Abstract	The developments of nanoparticle-based treatments that benefit from novel discoveries have an essential place in the regeneration of acute and chronic wounds. Furthermore, research about the treatment methods which attempt to swiftly and scarless wound recovery has increased over time. In recent years, it has been shown that metallic-based nanoparticles, especially silver and gold derived, have an accelerating effect on chronic and contaminated wound healing. The crucial factors of inducing and completion of regeneration of wound are enhanced epithelialization rate and neovascularization in the tissue. In our study, the main purpose is the investigation of the boosting effects of erbium borate nanoparticles on the wound healing process, especially scarless ones. Newly syntesized erbium borate nanoparticles (ErB-Nps) were characterized by their concentration and particle size using nanoparticle tracking analysis (NTA). In order to examine the effect of ErB-Np on wound closure, scratch assay for dermal epithelial cells and tube formation assay for endothelial cells were performed. In addition, in order to examine the effect of the ErB-Np at a molecular level, the levels of genes related to both wound healing, inflammation, and scarless wound closure were determined with the RT-PCR experiment. Consequently, it has been shown that erbium borate nanoparticles have increased the melioration speed of scar tissue and have given clues about scarless healing potential. The investigation of the regeneration potential of erbium borate nanoparticles was done via MTS assay, quantitative PCR analysis, reactive oxygen species assay, and scratch assay. Our results show that ErB-Np is a proper agent that can be used for scarless wound healing.
Keywords	angiogenesis ; borates ; epithelium ; erbium ; gold ; inflammation ; particle size ; quantitative polymerase chain reaction ; reactive oxygen species ; research ; silver ; trace elements
Language	English
Dates of publication	2021-09
Size	p. 3262-3271.
Publishing place	Springer US
Document type	Article
ZDB-ID	445336-0
ISSN	1559-0720 ; 0163-4984
ISSN (online)	1559-0720
ISSN	0163-4984
DOI	10.1007/s12011-020-02458-4
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: In vitro tooth-shaped scaffold construction by mimicking late bell stage.

TaŞli, Pakize Neslihan / YalÇin Ülker, Gül Merve / Cumbul, Alev / Uslu, Ünal / Yilmaz, Şahin / Bozkurt, Batuhan Turhan / Şahİn, Fikrettin

Turkish journal of biology = Turk biyoloji dergisi

2020 Volume 44, Issue 5, Page(s) 315–326

Abstract: Neogenesis of osseous and ligamentous interfacial structures is essential for the regeneration of large oral or craniofacial defects. However, current treatment strategies are inadequate in renewing supporting tissues of teeth after trauma, chronic ... ...

Abstract	Neogenesis of osseous and ligamentous interfacial structures is essential for the regeneration of large oral or craniofacial defects. However, current treatment strategies are inadequate in renewing supporting tissues of teeth after trauma, chronic infections or surgical resection. Combined use of 3D scaffolds with stem cells became a promising treatment option for these injuries. Matching different scaffolding materials with different tissues can induce the correct cytokines and the differentiation of cells corresponding to that particular tissue. In this study, a hydroxyapatite (HA) based scaffold was used together with human adipose stem cells (hASCs), human bone marrow stem cells (hBMSCs) and gingival epithelial cells to mimic human tooth dentin-pulp-enamel tissue complexes and model an immature tooth at the late bell stage in vitro. Characteristics of the scaffold were determined via SEM, FTIR, pore size and density measurements. Changes in gene expression, protein secretions and tissue histology resulting from cross-interactions of different dental tissues grown in the system were shown. Classical tooth tissues such as cementum, pulp and bone like tissues were formed within the scaffold. Our study suggests that a HA-based scaffold with different cell lineages can successfully mimic early stages of tooth development and can be a valuable tool for hard tissue engineering.
Language	English
Publishing date	2020-10-13
Publishing country	Turkey
Document type	Journal Article
ZDB-ID	2046470-8
ISSN	1303-6092 ; 1303-6092
ISSN (online)	1303-6092
ISSN	1303-6092
DOI	10.3906/biy-2002-19
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Effective Scarless Wound Healing Mediated by Erbium Borate Nanoparticles.

Kırbaş, Oğuz Kaan / Bozkurt, Batuhan Turhan / Taşlı, Pakize Neslihan / Hayal, Taha Bartu / Özkan, İrem / Bülbül, Berna / Beyaz, Seda / Şahin, Fikrettin

Biological trace element research

2020 Volume 199, Issue 9, Page(s) 3262–3271

Abstract	The developments of nanoparticle-based treatments that benefit from novel discoveries have an essential place in the regeneration of acute and chronic wounds. Furthermore, research about the treatment methods which attempt to swiftly and scarless wound recovery has increased over time. In recent years, it has been shown that metallic-based nanoparticles, especially silver and gold derived, have an accelerating effect on chronic and contaminated wound healing. The crucial factors of inducing and completion of regeneration of wound are enhanced epithelialization rate and neovascularization in the tissue. In our study, the main purpose is the investigation of the boosting effects of erbium borate nanoparticles on the wound healing process, especially scarless ones. Newly syntesized erbium borate nanoparticles (ErB-Nps) were characterized by their concentration and particle size using nanoparticle tracking analysis (NTA). In order to examine the effect of ErB-Np on wound closure, scratch assay for dermal epithelial cells and tube formation assay for endothelial cells were performed. In addition, in order to examine the effect of the ErB-Np at a molecular level, the levels of genes related to both wound healing, inflammation, and scarless wound closure were determined with the RT-PCR experiment. Consequently, it has been shown that erbium borate nanoparticles have increased the melioration speed of scar tissue and have given clues about scarless healing potential. The investigation of the regeneration potential of erbium borate nanoparticles was done via MTS assay, quantitative PCR analysis, reactive oxygen species assay, and scratch assay. Our results show that ErB-Np is a proper agent that can be used for scarless wound healing.
MeSH term(s)	Borates/pharmacology ; Endothelial Cells ; Erbium ; Nanoparticles ; Skin ; Wound Healing
Chemical Substances	Borates ; Erbium (77B218D3YE)
Language	English
Publishing date	2020-11-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	445336-0
ISSN	1559-0720 ; 0163-4984
ISSN (online)	1559-0720
ISSN	0163-4984
DOI	10.1007/s12011-020-02458-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Immunomodulatory Behavior of Mesenchymal Stem Cells.

Taşlı, Pakize Neslihan / Bozkurt, Batuhan Turhan / Kırbaş, Oğuz Kaan / Deniz-Hızlı, Ayşen Aslı / Şahin, Fikrettin

Advances in experimental medicine and biology

2018 Volume 1119, Page(s) 73–84

Abstract: The use of Mesenchymal Stem Cells (MSCs) in the treatment of diseases where immunomodulation impacts therapy is increasing steadily. Recent studies aim to achieve effective use of MSCs in treatment of Graft versus Host Disease (GvHD), Crohn's disease and ...

Abstract	The use of Mesenchymal Stem Cells (MSCs) in the treatment of diseases where immunomodulation impacts therapy is increasing steadily. Recent studies aim to achieve effective use of MSCs in treatment of Graft versus Host Disease (GvHD), Crohn's disease and organ transplantations. The molecular mechanisms governing immunomodulatory properties of MSCs have not been fully understood, although current studies are indicating progress. Especially, in vitro studies and animal models provide a major contribution to our knowledge in clinical use of MSCs. The immunosuppressive and immune-enhancer properties of MSCs are -typically- determined with respect to type and concentrations of soluble molecules found in their physiological environment. In mammals the immune system protects the organism -not only- from certain microorganisms, but also from any entity that it recognizes as foreign, including its own cells when it is received as a threat. This protection can sometimes occur by increasing the number of immune cells and sometimes by suppressing a pathologically hyper-induced immunological response. In particular, realization of the bi-directional effect of MSCs on immune cells has placed substantial emphasis on this area of research. This chapter focuses on the interaction of MSCs with the immune cells, the bilateral role of these interactions, and whether studies that aim to understand these interactions can yield promising results in terms of developing improved use of MSCs in treatment.
MeSH term(s)	Animals ; Graft vs Host Disease ; Immunomodulation ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells
Language	English
Publishing date	2018-08-22
Publishing country	United States
Document type	Journal Article
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/5584_2018_255
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A pilot study for treatment of severe COVID-19 pneumonia by aerosolized formulation of convalescent human immune plasma exosomes (ChipEXO™).

Gül, Fethi / Gonen, Zeynep Burcin / Jones, Olcay Y / Taşlı, Neslihan Pakize / Zararsız, Gökmen / Ünal, Ekrem / Özdarendeli, Aykut / Şahin, Fikrettin / Eken, Ahmet / Yılmaz, Semih / Karakukçu, Musa / Kırbaş, Oğuz Kaan / Gökdemir, Nur Seda / Bozkurt, Batuhan Turhan / Özkul, Yusuf / Oktay, Burçin Doruk / Uygut, Muhammet Ali / Cinel, Ismail / Çetin, Mustafa

Frontiers in immunology

2022 Volume 13, Page(s) 963309

Abstract: This is a single-center prospective, open-label, single arm interventional study to test the safety and efficacy of recently described ChipEXO™ for severe COVID-19 pneumonia. The ChipEXO™ is a natural product derived from convalescent human immune plasma ...

Abstract	This is a single-center prospective, open-label, single arm interventional study to test the safety and efficacy of recently described ChipEXO™ for severe COVID-19 pneumonia. The ChipEXO™ is a natural product derived from convalescent human immune plasma of patients recovered from moderate COVID-19 infection. In September 2021, 13 patients with pending respiratory failure were treated with ChipEXO™ adapted for aerosolized formulation delivered
MeSH term(s)	Humans ; COVID-19/therapy ; Pilot Projects ; Exosomes ; Prospective Studies ; Oxygen
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2022-11-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.963309
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